Oral isotretinoin was effective in the prevention of skin cancer and in the treatment of a variety of disorders of kertinization (lamellar ichthyosis, Darrier's disease, pityriasis rubra pilaris), and cystic acne. Oral etretinate was more effective and less toxic than isotretinoin in the treatment of the disorders of keratinization. A high initial dose followed by a low maintenance dose of isotretinoin was comparably effective but less toxic than previously used continuous high-dosage schedules in the treatment of cystic acne. Psychological testing revealed decreased anxiety and depression in cystic acne patients after treatment with isotretinoin. Isotretinoin and etretinate treatment led to small but significant elevations in plasma lipids and changes in lipoproteins, which were responsive to dietary management. Absorption of etretinate is greater with milk, as a source of long-chain fatty acids, than with water. Etretinate is stored in fat and persists in the serum after discontinuation of therapy; trace amounts have been detected after more than 3 years. One chronic toxicity, "retinoid hyperostosis," characterized by anterior spinal ligament calcification and osteophyte formation of vertebrae, has been observed in 80% of patients treated with long-term, high-dose isotretinoin. Sixty percent of acne patients with moderate doses of isotretinoin for 9 months also developed vertebral osteophytes. Seven patients with xeroderma pigmentosum were entered into a cancer chemoprevention study using isotretinoin. Of 5 patients entered into a phase I fenretinide-cancer chemoprevention study, 3 were discontinued due to toxicity (drug reaction, night blindness). Predominantly extraspinal tendon and ligament calcification occurred commonly after chronic therapy for psoriasis and disorders of keratinization with etretinate, an aromatic retinoid. The usual sites of involvement were the ankles, pelvis, and knees.